It is planned to investigate the structural properties of new and novel nucleosides and nucleotides with potential therapeutic properties using circular dichroism spectroscopy, nuclear magnetic resonance spectroscopy and quantum chemical conformational computations. The proposed research is designed to complement the synthesis and biochemical studies underway in the laboratory of Professor Roland K. Robins, co-investigator. Several series of compunds which encompass structurally modified nucleosides and nucleotides will be studied including the nucleoside tunicamycin and derivatives of related antiviral antibiotics, nucleoside- and nucleotide-peptides and related derivatives, and 3',5'-cyclic nucleotide derivatives. The specific objectives are: (1) To characterize the nucleoside and nucleotide analogs with respect to optical activity and NMR parameters in various media environments; (2) To determine the preferred conformational states of the nucleoside and nucleotide analogs from empirical and theoretical analysis of the circular dischroism and NMR data; (3) To determine the electronic structure and conformational domains of the nucleoside and nucleotide analogs from quantum mechanical calculations; (4) To combine the detailed geometry, stereochemistry, and electronic structure of nucleoside analogs with results from biochemical studies to establish or support structure-activity relationships.